Pharmacology

Imidapril is an angiotensin-converting enzyme (ACE) inhibitor.

Pharmacodynamic properties:

Imidapril is a pro-drug which is hydrolysed in the body to form an active metabolite, imidaprilat. Imidaprilat inhibits the angiotensin-converting enzyme (ACE). This enzyme catalyses the conversion of angiotensin I to angiotensin II in the blood plasma and endothelia and prevents the breakdown of bradykinin. As angiotensin II has a potent vasoconstrictive action, while bradykinin is a vasodilator, the reduced formation of angiotensin II and the inhibition of bradykinin breakdown leads to vasodilation. In addition, plasma angiotensin II causes the release of aldosterone in the renin-angiotensin-aldosterone system. Imidaprilat therefore reduces the secretion of aldosterone. This leads to an increase in the serum potassium concentration and a decrease in the serum sodium concentration. So, imidapril reduces heart preload and after load, and increases cardiac output without any compensatory increase in the heart rate arising.

Pharmacokinetic properties:

Pharmacokinetic parameters of imidapril and imidaprilat in fasted dogs after a single dose of 0.25 mg/kg of Prilium®300 mg

Parameter

Imidapril

Imidaprilat

Tmax (h)

0.47

6.00

Cmax (ng/mL)

22.21

14.18

T1/2λz (h)

2.18

12.86

AUClast (ng•h/mL)

40.94

208.5

Following oral administration in the dog, imidapril is rapidly absorbed from the gastrointestinal tract and reaches its maximum plasma concentration within less than one hour. Plasma concentration decline with a half-life of about 2 hours. Imidapril is mainly hydrolyzed in the liver and kidney to its pharmacologically active metabolite, imidaprilat. Maximum plasma concentrations of imidaprilat are reached within about 6 hours and decline with a mean apparent last elimination half-life of more than 10 hours. The protein binding of imidapril and imidaprilat was moderate (85% and 59%, respectively). After oral administration of the radio-labelled compound about 40% of total radioactivity is excreted in urine and about 60% in the faeces. Food administration decreases the concentrations of imidapril and imidaprilat.

After multiple dosing, there is no accumulation of imidapril and imidaprilate reaches steady-state after 3 days.

Prilium 75 mg Indication

Prilium® is indicated for the treatment of clinical signs of congestive heart failure caused by mitral regurgitation or dilated cardiomyopathy in dogs. Prilium® can be used in combination with standard therapy.

Prilium 75 mg Dosage And Administration

The recommended dose of imidapril is 0.25 mg/kg once a day orally or:

Formulation

Strength when reconstituted

Weight range of dog

Dose to be administered

Prilium®75 mg

2.5 mg/mL

< 7.5 kg

0.1 mL/kg

Prilium®150 mg

5 mg/mL

7.5-30 kg

0.05 mL/kg

Prilium®300 mg

10 mg/mL

> 30 kg

0.025 mL/kg

Note: administering imidapril with food may decrease its absorption.

RECONSTITUTION OF THE SOLUTION

1. Remove the rubber cap from the vial.

2. Fill the vial to the raised line with potable water (total solution volume of 30 mL).

3. Close the bottle with the child-proof cap.

4. Shake well.

5. Remove the child-proof cap and insert the syringe in the remaining adapter.

6. Withdraw the required quantity of medication.

Note: This product can cause eye or skin irritation. Avoid contact with eyes or skin. Wash hands with water after reconstitution of the solution or handling of the product. People with history of sensitivity should avoid handling the product.

Contraindications

Not to be used in case of low blood pressure. Not to be used in case of acute renal failure. Not to be used in patients who have demonstrated a hypersensitivity to ACE inhibitors.

Drug Interactions

The concomitant use of imidapril with diuretics and/or other vasodilators may potentially cause hypotension. Concomitant use of imidapril and potassium or potassium sparing diuretics such as spironolactone may result in hyperkalemia.

Adverse Reactions

Diarrhea, hypotension and related symptoms such as fatigue, dizziness or anorexia can occur. In such cases treatment should be discontinued until the patient’s condition has returned to normal.

Vomiting, coughing, azotemia, decrease appetite, syncope and AV block have also been seen in the clinical trial. Rare cases of angioedema have been reported post-approval in Europe.

Prilium 75 mg Cautions

The use of ACE inhibitors in dogs with hypovolaemia/dehydration can lead to acute hypotension. In such cases the fluid and electrolyte balance should be restored immediately and treatment suspended until it has been stabilized. Renal function should be monitored in all dogs during therapy. Dogs with azotemia and renal disease should be monitored more frequently. The dose of diuretics and/or imidapril may need to be reduced or discontinued if signs of hypotension or azotemia develop.

The safety of Prilium® in dogs during breeding, pregnancy and lactation has not been established. Thus, Prilium® is not recommended in breeding, pregnant or lactating dogs.

Overdose

Oral doses of up to 5 mg/kg of imidapril (20 times the recommended dose) given for 13 weeks were well tolerated in healthy young dogs. Hypotension may occur as a symptom of overdose with signs of apathy and ataxia. The treatment is symptomatic.

Warnings

Keep out of reach of children. Avoid contact with skin and eyes.

If contact occurs rinse well with water. If irritation persists seek medical attention.

Storage

Before reconstitution: store between 15°C and 25°C.

After reconstitution: store between 4°C and 8°C (refrigerator). The reconstituted solution is stable for 77 days at 5°C.

Every effort has been made to ensure the accuracy of the Prilium 75 mg information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.